Leithner Doris, Flynn Jessica R, Devlin Sean M, Mauguen Audrey, Fei Teng, Zeng Shang, Zheng Junting, Imber Brandon S, Hubbeling Harper, Mayerhoefer Marius E, Bedmutha Akshay, Luttwak Efrat, Corona Magdalena, Dahi Parastoo B, Luna de Abia Alejandro, Landego Ivan, Lin Richard J, Palomba M Lia, Scordo Michael, Park Jae H, Tomas Ana Alarcon, Salles Gilles, Lafontaine Daniel, Michaud Laure, Shah Gunjan L, Perales Miguel-Angel, Shouval Roni, Schöder Heiko
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA.
Department of Radiology, NYU Grossman School of Medicine, New York, USA.
J Hematol Oncol. 2024 Apr 23;17(1):21. doi: 10.1186/s13045-024-01540-x.
Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T F-fluorodeoxyglucose positron emission tomography/computed tomography ([F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes. At both pre-apheresis and pre-infusion time points, conventional PET features of disease correlated with elevated inflammatory markers. At pre-infusion, MTV was associated with grade ≥ 2 cytokine release syndrome (odds ratio [OR] for 100 mL increase: 1.08 [95% confidence interval (CI), 1.01-1.20], P = 0.031), and SUVmax was associated with failure to achieve complete response (CR) (OR 1.72 [95% CI, 1.24-2.43], P < 0.001). Higher pre-apheresis and pre-infusion MTV values were associated with shorter progression-free survival (PFS) (HR for 10-unit increase: 1.11 [95% CI, 1.05-1.17], P < 0.001; 1.04 [95% CI, 1.02-1.07], P < 0.001) and shorter overall survival (HR for 100-unit increase: 1.14 [95% CI, 1.07-1.21], P < 0.001; 1.04 [95% CI, 1.02-1.06], P < 0.001). A combined MTV and LDH measure stratified patients into high and low PFS risk groups. Multiple pre-infusion novel radiomic features were associated with CR. These quantitative conventional [F]FDG PET/CT features obtained before CAR-T cell infusion, which were correlated with inflammation markers, may provide prognostic biomarkers for CAR-T therapy efficacy and toxicity. The use of conventional and novel radiomic features may thus help identify high-risk patients for earlier interventions.
复发和毒性限制了嵌合抗原受体T细胞（CAR-T）疗法对大B细胞淋巴瘤（LBCL）的疗效，但目前缺乏能够预测疗效和毒性的生物标志物。我们研究了180例患者（121例男性；中位年龄66岁）在接受CAR-T治疗前的F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（[F]FDG PET/CT）扫描（n = 341）中提取的放射组学特征。评估了3种传统特征（最大标准化摄取值[SUVmax]、代谢肿瘤体积[MTV]、总病变糖酵解[TLG]）和116种新的放射组学特征，以及炎症标志物、毒性和疗效。在采集前和输注前两个时间点，疾病的传统PET特征与炎症标志物升高相关。在输注前，MTV与≥2级细胞因子释放综合征相关（每增加100 mL的优势比[OR]：1.08[95%置信区间（CI），1.01 - 1.20]，P = 0.031），而SUVmax与未达到完全缓解（CR）相关（OR 1.72[95%CI，1.24 - 2.43]，P < 0.001）。采集前和输注前较高的MTV值与较短的无进展生存期（PFS）相关（每增加10个单位的风险比[HR]：1.11[95%CI，1.05 - 1.17]，P < 0.001；1.04[95%CI，1.02 - 1.07]，P < 0.001）和较短的总生存期（每增加100个单位的HR：1.14[95%CI，1.07 - 1.21]，P < 0.001；1.04[95%CI，1.02 - 1.06]，P < 0.001）。MTV和乳酸脱氢酶（LDH）的联合测量将患者分为高PFS风险组和低PFS风险组。多个输注前的新放射组学特征与CR相关。这些在CAR-T细胞输注前获得的定量传统[F]FDG PET/CT特征与炎症标志物相关，可能为CAR-T治疗的疗效和毒性提供预后生物标志物。因此，使用传统和新的放射组学特征可能有助于识别高危患者以便进行早期干预。
